Accumulation of insoluble tau protein in the CNS of mice. A, B, Neocortical (A) and spinal cord (B) tissues of 6-month-old mice from each group were sequentially extracted with RAB, RIPA buffer, and 70% FA, and the tau levels were determined by quantitative Western blot analysis with antibody 17026.C, D, Alteration in the FA-soluble tau as a percentage of total tau in the neocortex (C) and spinal cord (D) of T44 tau-overexpressing mice. The percentage was calculated from quantitative Western blot analysis at 6 and 12 months of age (n = 3). The amount of FA-soluble fraction as a percentage of total tau protein in T44;NFL−/− mice was significantly decreased (*p< 0.01) compared with that of T44 mice at 6 month of age, and it increased by 90.2% (neocortex) and 77.6% (spinal cord) at 12 months of age, whereas the increase in the other group of mice was 17.5–42.9%.